Preview

Fine Chemical Technologies

Advanced search

An effective method for preparation of high purity oligohexamethylene guanidine salts

https://doi.org/10.32362/2410-6593-2020-15-3-31-38

Full Text:

Abstract

Objectives. Given that microorganisms can become resistant to certain groups of drugs and considering also their ability to form biofilms, the development of new drugs that are active against adapted microflora is required. This study focused on the development of a new method for the synthesis of a promising compound, the branched hydrosuccinate oligohexamethylene guanidine (OHMGsucc), with high purity that meets the standards of the 14th edition State Pharmacopeia of the Russian Federation (SPRF). Previously proposed methods have managed to isolate this product, which, however, complies with the requirements of the outdated SPRF. Therefore, the main aim of this study was to update the regulatory framework for the indicated OHMG salt for its further use in the pharmaceutical industry according to modern standards.

Methods. To control the residual impurities of hexamethylenediamine (HMDA) and guanidine hydrochloride (GHC), high-performance liquid chromatography (HPLC) was applied using a Thermo Scientific Dionex UltiMate 3000 chromatograph, and the chromatographic signals of the test solution with those of a standard sample solution obtained by a previously published conventional method were compared.

Results. The HPLC experimental data indicated a significant difference in the quantitative content of HMDA and GHC observed for the new and older preparation method of the branched OHMGsucc, suggesting that the method disclosed in this article can be used to obtain highly pure OHMGsucc.

Conclusions. The specified compound was standardized with the parameter “related impurities” according to the current (14th) edition of the SPRF. The effectiveness and reproducibility of the proposed method was experimentally confirmed. In addition, a process diagram for the preparation of the indicated OHMG salt was prepared.

About the Authors

I. S. Ivanov
MIREA – Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies); Institutе of Рhаrmасеutiсаl Тесhnоlоgiеs
Russian Federation

Ivan S. Ivanov, Postgraduate Student, Department of Biotechnology and Industrial Pharmacy

86, Vernadskogo pr., Moscow, 119571



D. O. Shatalov
MIREA – Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies); Institutе of Рhаrmасеutiсаl Тесhnоlоgiеs
Russian Federation

Denis O. Shatalov, Cand. of Sci. (Pharmaceutical Science), Associate Professor, Department of Biotechnology and Industrial Pharmacy

86, Vernadskogo pr., Moscow, 119571



S. A. Kedik
MIREA – Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies); Institutе of Рhаrmасеutiсаl Тесhnоlоgiеs
Russian Federation

Stanislav A. Kedik, Dr. of Sci. (Engineering), Professor, Head of the Department of Biotechnology and Industrial Pharmacy, General Director of the Institute of Pharmaceutical Technologies JSC

86, Vernadskogo pr., Moscow, 119571



I. P. Sedishev
MIREA – Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies); Institutе of Рhаrmасеutiсаl Тесhnоlоgiеs
Russian Federation

Igor P. Sedishev, Cand. of Sci. (Chemistry), Associate Professor, Department of Biotechnology and Industrial Pharmacy

86, Vernadskogo pr., Moscow, 119571



S. V. Beliakov
MIREA – Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies); Institutе of Рhаrmасеutiсаl Тесhnоlоgiеs
Russian Federation

Sergei V. Beliakov, Postgraduate Student, Department of Biotechnology and Industrial Pharmacy

86, Vernadskogo pr., Moscow, 119571



K. N. Trachuk
MIREA – Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies)
Russian Federation

Kirill N. Trachuk, Student, Department of Biotechnology and Industrial Pharmacy

86, Vernadskogo pr., Moscow, 119571



V. V. Komarova
MIREA – Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies)
Russian Federation

Victoria V. Komarova, Student, Department of Biotechnology and Industrial Pharmacy

86, Vernadskogo pr., Moscow, 119571



References

1. Dieleman J.L., Schneider M.T., Singh L., Sadat N., Birger M., Reynolds A., Templin T., Hamavid H., Chapin A., Murray C.J.L., Haakenstad A. Development assistance for health: past trends, associations, and the future of international financial flows for health. The Lancet. 2016;387(10037):2536-2544. https://doi.org/10.1016/S0140-6736(16)30168-4

2. Sadekuzzaman M., Yang S., Mizan M.F.R., Ha S.D. Current and recent advanced strategies for combating biofilms. Compr. Rev. Food Sci. F. 2015;14(4):491-509. https://doi.org/10.1111/1541-4337.12144

3. Vointseva I.I., Gembitsky P.A. Poliguanidiny dezinfektsionnye sredstva i polifunktsional’nye dobavki v kompozitsionnye materialy (Polyguanidines - disinfectants and multifunctional additives in composite materials). Moscow: LKM-Press Publishing House, 2009; 304 p. (in Russ). ISBN 978-5-9901286-2-0

4. Zhou Z.X., Wei D.F., Guan Y., Zheng A.N., Zhong J.J. Damage of Escherichia coli membrane by bactericidal agent polyhexamethylene guanidine hydrochloride: Micrographic evidences. J. Appl. Microbiol. 2010;108(3):898-907. http://dx.doi.org/10.1111/j.1365-2672.2009.04482.x

5. Kedik S.A., Sedishev I.P., Panov A.V., Zhavoronok E.S., Kha K.A. Branched oligomers based on a guanidine derivative and a disinfectant containing them: RF Pat. 2443684. Publ. 27.02.2012 (in Russ.).

6. Rodlovskaya E.N., Izmailov B.A., Vasnev V.A., Mishina E.S. Protection of Textile Materials against Biodamage. Immobilization of Oligohexamethylene Guanidine Hydrochloride on the Surface of Fiber. International Polymer Science and Technology. 2013;40(6):39-42. https://doi.org/10.1177/0307174X1304000608

7. Garcia I.M., Rodrigues S.B., Leitune C.B., Collares F.M. Antibacterial, chemical and physical properties of sealants with polyhexamethylene guanidinehydrochloride. Braz. Oral Res. 2019;33(0). https://doi.org/10.1590/1807-3107bor-2019.vol33.0019

8. Shatalov D.O., Kedik S.A., Aidakova A.V., Krupenchenkova N.V., Kovalenko A.V., Ivanov I.S. Current approaches to the development of dosage forms for the treatment of diseases of the oral cavity (review). Biofarmatsevticheskii Zhurnal = Russian Journal of Biopharmaceuticals. 2019;11(4):15-28 (in Russ.).

9. Shatalov D.O., Kedik S.A., Panov A.V., Aidakova A.V., Ivanov I.S., Belyakov S.V. The combined drug in the form of a solution for obtaining a spray for the treatment of diseases of the oral cavity: RF Pat. 2687745. Publ. 16.05.2019 (in Russ.).

10. Kha K.A., Grammatikova N.E., Vasilenko I.A., Kedik S.A. Comparative in vitro Antibacterial Activity of Polyhexamethylene Guanidine Hydrochloride and Polyhexamethylene Guanidine Succinate. Antibiotics and Chemotherapy. 2013;(58):3-7. PMID: 24640138.

11. Kha K.A. Development of a technology for producing a substance of oligoghexamethylene guanidine hydrosuccinate and eye drops based on it: Dis. Cand. Sci. Farm. Moscow, 2013. 131 p. (in Russ.).


Supplementary files

1. Effect of OHMG on a bacterial cell.
Subject
Type Research Materials
View (915KB)    
Indexing metadata
2. This is to certify that the paper titled An effective method for preparation of high purity oligohexamethylene guanidine salts commissioned to Enago by Ivan S. Ivanov, Denis O. Shatalov, Stanislav A. Kedik, Igor P. Sedishev, Sergei V. Beliakov, Kirill N. Trachuk, Victoria V. Komarova has been edited for English language and spelling by Enago, an editing brand of Crimson Interactive Inc.
Subject CERTIFICATE OF EDITING
Type Other
View (421KB)    
Indexing metadata
  • An alternative method for the purification of a guanidine derivative with promising antiseptic properties has been proposed.
  • The specified purification method results in a reduction in the content of residual monomers.
  • The described purification method enables synthesis of branched hydrosuccinate oligohexamethylene guanidine exhibiting high purity, which meets the standards of the 14th edition State Pharmacopeia of the Russian Federation.

For citation:


Ivanov I.S., Shatalov D.O., Kedik S.A., Sedishev I.P., Beliakov S.V., Trachuk K.N., Komarova V.V. An effective method for preparation of high purity oligohexamethylene guanidine salts. Fine Chemical Technologies. 2020;15(3):31-38. https://doi.org/10.32362/2410-6593-2020-15-3-31-38

Views: 122


ISSN 2410-6593 (Print)
ISSN 2686-7575 (Online)